Use of whole-body autoradiography in cancer targeting with radiolabeled antibodies.
Methods of single-tracer whole-body autoradiography (WBAR) have been developed in our laboratory which allow imaging and measurement of the zonal distribution of radioiodinated antibodies and their fragments within GW-39 colon carcinoma xenografts varying in size from large, cystic masses with necrotic cores to micrometastases. The whole-animal distribution of 90Y-labeled anti-carcinoembryonic antigen monoclonal antibody NP-2 was evaluated by WBAR in nude mice bearing s.c. implants of GW-39 colon cancer and revealed antitumor uptake specifically as well as significant accumulation of 90Y in the bones. Dual-tracer qualitative WBAR methods have also been applied in order to examine the biodistribution of labeled immunoglobulins in the GW-39 animal tumor model as a function of the underlying rapid cell proliferation index ([3H]-thymidine assay) in the same tumor. In addition, extension of the WBAR method was made to permit imaging of the biodistribution of 10B compounds in mice bearing Harding-Passey melanoma implants by using a track-etch procedure to produce alpha-particle WBAR. Further applications of single and multiple radionuclide WBAR are offered and discussed as an effective means of assessing the degree of penetration of immunoglobulins in tumors in which vascular patterns, local glucose metabolism, protein synthesis, and rapid cell proliferation indices may be characterized.
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Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Sharkey
R M
RM
Goldenberg
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal; D001345:Autoradiography; D001895:Boron; D002272:Carcinoembryonic Antigen / Q000276:immunology; D006224:Cricetinae; D007140:Immunoglobulin Fab Fragments / Q000032:analysis; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D015021:Yttrium Radioisotopes; D001895:Boron